TrkB

STOCKHOLM, SWEDEN / ACCESSWIRE / October 25, 2023 / AlzeCure Pharma (STO:ALZCUR)(FRA:AC6) AlzeCure Pharma AB (publ) (FN STO: ALZCUR), a pharmaceutical company that develops drug candidates for CNS diseases, focusing on Alzheimer's disease and pain, today announced that the company's presentation at the Alzheimer's conference CTAD 2023 is now available in its entirety on the company's website. The presentation contains new preclinical data with its leading clinical drug candidate NeuroRestore ACD856, which is being developed with a focus on Alzheimer's disease. "These new preclinical data provide further support for a potential disease-modifying effect of NeuroRestore ACD856. This, together with the previously observed memory-enhancing effects, shows a broad potential for this drug candidate," said Pontus Forsell, Head of Discovery and Research at AlzeCure Pharma. The presentation, titled NeuroRestore ACD856, a Trk-PAM in clinical development for Alzheimer's disease shows neuroprotective and neurorestorative effects , was held by Martin Jönsson, CEO at AlzeCure Pharma, and includes new preclinical data with ACD856, the lead clinical drug candidate in the NeuroRestore platform. The results from the new preclinical studies with ACD856 show, among other things, that the substance can protect nerve cells against toxic Ab42, the protein that forms amyloid plaques in the brains of Alzheimer's patients. Furthermore, growth-stimulating effects on neurons were observed with ACD856. These effects have specific relevance to Alzheimer's disease, where dysfunction and loss of neurons are important key findings in the disease. ACD856, which is a positive modulator of both NGF/TrkA- and BDNF/TrkB-mediated signaling, has been shown in previous preclinical studies to improve learning and memory and is being developed primarily for the treatment of Alzheimer's disease. The drug candidate has undergone phase I clinical studies, where both good safety and tolerability were demonstrated in humans, but also that the drug candidate crossed the blood-brain barrier and that the substance activated parts of the brain that are central to both cognition and depression treatment. "These new results with NeuroRestore ACD856 strengthen the commercial potential of the project. The findings are not only relevant for Alzheimer's, but also for other neurodegenerative diseases, such as Parkinson's and frontal lobe dementia," said Martin Jönsson. The poster is available on AlzeCure's website: . For more information, please contact Martin Jönsson, CEO Tel: +46 707 86 94 43 martin.jonsson@alzecurepharma.com About AlzeCure Pharma AB (publ) AlzeCure® is a Swedish pharmaceutical company that develops new innovative small molecule drug therapies for the treatment of severe diseases and conditions that affect the central nervous system, such as Alzheimer's disease and pain - indications for which currently available treatment is very limited. The company is listed on Nasdaq First North Premier Growth Market and is developing several parallel drug candidates based on three research platforms: NeuroRestore®, Alzstatin® and Painless. NeuroRestore consists of two symptomatic drug candidates where the unique mechanism of action allows for multiple indications, including Alzheimer's disease, as well as cognitive disorders associated with traumatic brain injury, sleep apnea and Parkinson's disease, as well as for depression treatment. The Alzstatin platform focuses on developing disease-modifying and preventive drug candidates for early treatment of Alzheimer's disease and comprises two drug candidates. Painless is the company's research platform in the field of pain and contains two projects: ACD440, which is a drug candidate in the clinical development phase for the treatment of neuropathic pain, and TrkA-NAM, which targets severe pain in conditions such as osteoarthritis. AlzeCure aims to pursue its own projects through preclinical research and development through an early clinical phase, and is continually working on business development to find suitable outlicensing solutions, alternatively partnership, with other pharmaceutical companies. FNCA Sweden AB is the company's Certified Adviser. For more information, please visit . About NeuroRestore NeuroRestore is a platform of symptom-relieving drug candidates for disease states in which cognitive ability is impaired, e.g. Alzheimer's Disease, sleep apnea, traumatic brain injury and Parkinson's disease. NeuroRestore stimulates several important signaling pathways in the brain, which among other things leads to improved cognition. Preclinical studies with NeuroRestore have shown that AlzeCure's drug candidates enhance communication between the nerve cells and improve cognitive ability. The NeuroRestore substances are so called Trk-PAMs which stimulate specific signaling pathways in the central nervous system known as neurotrophins, the most well-known being NGF (Nerve Growth Factor) and BDNF (Brain Derived Neurotrophic Factor). The levels of NGF and BDNF are disturbed in several disease states and the signaling is reduced. The impaired function impairs communication between the synapses, i.e. the contact surfaces of the nerve endings, as well as reducing the possibility of survival for the nerve cells, which gives rise to the cognitive impairments. Neurotrophins play a crucial role for the function of nerve cells, and a disturbed function of BDNF has a strong genetic link to impaired cognitive ability in several different diseases, such as Alzheimer's, Parkinson's disease, traumatic brain injury and sleep disorders. In addition to cognitive-enhancing effects, new preclinical data also show that NeuroRestore substances have a positive effect on mitochondrial function and cell survival, which could indicate potential disease-modifying effects. The leading drug candidate in the platform, ACD856, has recently completed clinical phase I studies and demonstrated positive effects there that support continued development of the program. There is also a connection between BDNF signaling and depression, something that has been further strengthened in recent years. AlzeCure has been able to show in preclinical models that NeuroRestore substances have antidepressant effects, which are further strengthened by data in recently published articles in the well-respected journals Cell, Nature and Science. These studies show that several different classes of antidepressants appear to mediate their effects via BDNF/TrkB, further strengthening the link between BDNF and depression. About Alzheimer's disease Alzheimer's disease is the most common form of dementia, affecting approximately 45 million people worldwide. Alzheimer's disease is a lethal disorder that also has a large impact on both relatives and the society. Today, preventive and disease modifying treatments are missing. The main risk factors to develop Alzheimer's are age and genetic causes. Even though the disease can start as early as between 40 and 65 years of age, it is most common after 65 years. Significant investments in Alzheimer research are being made because of the significant unmet medical need and the large cost of this disease for healthcare and society. The total global costs for dementia related diseases is estimated to about 1,300 billion USD globally in 2019 and is expected to triple over the next 30 years as the average life expectancy is expected to continue to increase. Given the lack of both effective symptomatic treatments and disease modifying treatments, the need for new effective therapies is acute.The few approved drugs on the market today have only a limited symptomatic effect and can produce dose limiting side effects. A disease modifying treatment for Alzheimer's disease is estimated to reach more than $15 billion in global annual sales. In Sweden, approximately 100,000 people suffer from Alzheimer's disease with a healthcare cost of about SEK 63 billion yearly, which is more than for cancer and cardiovascular diseases combined. Image Attachments Pontus Forsell Head Of DnR Johan Sandin CSO Martin Jönsson CEO AlzeCure Attachments AlzeCure presents disease-modifying data with NeuroRestore ACD856 at Alzheimer's conference CTAD SOURCE: AlzeCure Pharma View source version on accesswire.com:

Foundation Medicine’s tissue-based comprehensive genomic profiling test is now FDA approved to identify patients with solid tumors with RET gene fusions who may benefit from treatment with Retevmo CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Foundation Medicine Inc. today announced that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOne®CDx to be used as a companion diagnostic for Eli Lilly and Company's Retevmo (selpercatinib), which was approved by the FDA for the treatment of adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. This announcement marks Foundation Medicine’s fifth pan-tumor approval in the U.S. for FoundationOne CDx, the only tissue test with multiple biomarkers approved as a tumor agnostic companion diagnostic in the U.S., including TMB and NTRK1/2/3. It also marks Foundation Medicine’s ninth approved companion diagnostic indication across 7 different fusion genes (ALK, ROS1, NTRK1, NTRK2, NTRK3, FGFR2, and now RET.) Using a tissue sample, FoundationOne CDx analyzes more than 300 cancer-related genes for genomic alterations in a patient’s tumor, which allows a tailored treatment approach and will determine if Retevmo is an appropriate treatment option for patients with RET gene fusions, which occur in less than two percent of solid tumors1. The test currently has over 30 companion diagnostic indications, ranging from lung, breast, prostate, colon, and other solid malignancies. “With a growing need for solutions for patients with rare fusions, high-quality companion diagnostics provide critical information to support oncologists in the development of personalized treatment plans,” said Mia Levy, MD, PhD, chief medical officer at Foundation Medicine. “With our experience successfully navigating the complexities of a pan-tumor approval, we’re proud to have another companion diagnostic for our FDA-approved tissue test that can help enable broader access to an important therapy option for RET-fusion positive solid tumors. We appreciate this meaningful collaboration with Lilly to help bring more treatment options to patients facing a cancer diagnosis.” “One of our top priorities is helping people living with lung cancer access the best treatment possible and this approval marks a milestone on the path to developing highly personalized care for them,” said GO2 for Lung Cancer President & CEO Laurie Ambrose. “We are encouraged by the expanded access and options they will receive and are confident this will positively impact the lives of people living with cancer and their loved ones.” Foundation Medicine is the global leader in companion diagnostic approvals. The company also has 60% of all U.S. companion diagnostic approvals for next generation sequencing (NGS) testing. This companion diagnostic approval is the latest in a series of collaborative efforts between Foundation Medicine and Lilly. Foundation Medicine® and FoundationOne® are registered trademarks of Foundation Medicine, Inc. Retevmo® is a registered trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates. About FoundationOne CDx FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit . About Foundation Medicine: Your Essential Partner in Cancer Care Foundation Medicine is a pioneer in molecular profiling for cancer, working to shape the future of clinical care and research. We collaborate with a broad range of partners across the cancer community and strive to set the standard for quality, scientific excellence, and regulatory leadership. Our deep understanding of cancer biology helps physicians make informed treatment decisions for their patients and empowers researchers to develop new medicines. Every day, we are driven to help our partners find answers and take action, enabling more people around the world to benefit from precision cancer care. For more information, please visit us on and follow us on Twitter and LinkedIn. Source: Foundation Medicine _______________________________ 1 .

WHIPPANY, N.J.--( BUSINESS WIRE )--Bayer announced data from three distinct Vitrakvi ® (larotrectinib) post-hoc subgroup analyses. The data was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting from June 2-6, 2023. Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Patients should be selected for therapy based on a Food and Drug Administration (FDA)-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 4 “ These findings reinforce Vitrakvi’s ability to treat patients with NTRK fusion-positive cancer and the importance of targeting the oncogenic driver,” said Iain Webb, M.D., Vice President, U.S. Medical Affairs, Oncology at Bayer. “ Testing patients comprehensively and early is pivotal to finding patients with NTRK fusion tumors and treating appropriate patients with Vitrakvi.” Larotrectinib long-term efficacy and safety in adult patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer (Abstract 3141) 1 In post-hoc subgroup analyses (data cut-off July 2022) of adult patients (n=180) with TRK fusion cancer across 24 different tumor types, including patients with central nervous system (CNS) metastases (n=22), Vitrakvi demonstrated an objective response rate (ORR) of 57% (95% CI 50-65) {16% (n=29) complete responses (including one pathological complete response) and 41% (n=74) partial responses}. In evaluable patients with CNS metastases (n=22), ORR was 68% (95% CI 45-86). Among all patients, median time to response was 1.8 months and median duration of response (DoR) was 43.3 months (95% CI 29.2-not estimable [NE]) at a median follow-up of 32.3 months. Treatment-related adverse events (TRAEs) were predominantly Grade 1-2, with Grade 3-4 occurring in 14% (n=27) of patients. Responses were assessed by IRC. Long-term efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer (Abstract 9056) 2 In an expanded dataset (n=30) with longer follow-up, Vitrakvi demonstrated long-term efficacy and safety data in adult patients with advanced TRK fusion lung cancer, including those with CNS metastases (n=12). The results encourage wider adoption of next-generation sequencing (NGS) testing for identifying patients with solid tumors harboring NTRK gene fusions, including lung cancer. Among 27 adult patients eligible for IRC assessment with TRK fusion lung cancer enrolled, ORR was 74% (95% CI 54-89); 11% (n=3) complete responses and 63% (n=17) partial responses. Among the 12 patients with baseline CNS metastases, the ORR was 67% (95% CI 35-90), with 8 partial responses. Median DoR was 33.9 months (95% CI 9.5-NE); median follow-up was 22.9 months. TRAEs were predominantly for Grade 1-2. Grade 3-4 TRAEs were reported in 5 patients which included AST increase, ALT increase, myalgia, and hypersensitivity. Larotrectinib (laro) long-term efficacy and safety in patients (pts) with tropomyosin receptor kinase (TRK) fusion thyroid carcinoma (TC) (Abstract 6091) 3 Vitrakvi was evaluated in updated subgroup analyses of patients (n=30; data cut-off July 20, 2022) with TRK fusion thyroid cancer (TC). Among those eligible for efficacy assessment, 47% (n=14) had NTRK1 and 53% (n=16) had NTRK2 . Fifty percent (n=15) of patients received no prior systemic therapies, 20% (n=6) received ≥2, and 77% (n=23) received prior radioiodine. ORR was 63% (95% CI 44-80); 10% (n=3) complete responses and 53% (n=16) partial responses. For patients classified as differentiated thyroid cancer (DTC; n=23), ORR was 78% (95% CI 56-93). For patients classified as anaplastic thyroid cancer (ATC; n=7), ORR was 14% (95% CI 0-58). All patients with CNS metastases (n=4) at baseline had a partial response. Median time to response was 1.9 months and median DoR was 43.3 months (95% CI 21.6-NE) at a median follow-up of 32.3 months. Grade ≥3 TRAEs, anemia and decreased lymphocycte count, were reported in 7% (n=2) patients. There were no treatment discontinuations due to TRAEs. Responses were assessed by IRC. About Vitrakvi ® (larotrectinib) 4 Vitrakvi ® (larotrectinib) is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase ( NTRK ) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection will likely result in severe morbidity, and have no satisfactory alternative treatments or that have progressed following treatment. Select patients for therapy based on an FDA-approved test. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. IMPORTANT SAFETY INFORMATION Warnings and Precautions Central Nervous System Effects: Central nervous system (CNS) adverse reactions occurred in patients receiving VITRAKVI, including dizziness, cognitive impairment, mood disorders, and sleep disturbances. In patients who received VITRAKVI, all grades CNS effects including cognitive impairment, mood disorders, dizziness and sleep disorders were observed in 42% with Grades 3-4 in 3.9% of patients. Cognitive impairment occurred in 11% of patients. The median time to onset of cognitive impairment was 5.6 months (range: 2 days to 41 months). Cognitive impairment occurring in ≥ 1% of patients included memory impairment (3.6%), confusional state (2.9%), disturbance in attention (2.9%), delirium (2.2%), cognitive disorders (1.4%), and Grade 3 cognitive adverse reactions occurred in 2.5% of patients. Among the 30 patients with cognitive impairment, 7% required a dose modification and 20% required dose interruption. Mood disorders occurred in 14% of patients. The median time to onset of mood disorders was 3.9 months (range: 1 day to 40.5 months). Mood disorders occurring in ≥1% of patients included anxiety (5%), depression (3.9%), agitation (2.9%), and irritability (2.9%). Grade 3 mood disorders occurred in 0.4% of patients. Dizziness occurred in 27% of patients, and Grade 3 dizziness occurred in 1.1% of patients. Among the 74 patients who experienced dizziness, 5% of patients required a dose modification and 5% required dose interruption. Sleep disturbances occurred in 10% of patients. Sleep disturbances included insomnia (7%), somnolence (2.5%), and sleep disorder (0.4%). There were no Grade 3-4 sleep disturbances. Among the 28 patients who experienced sleep disturbances, 1 patient each (3.6%) required a dose modification or dose interruption. Advise patients and caretakers of these risks with VITRAKVI. Advise patients not to drive or operate hazardous machinery if they are experiencing neurologic adverse reactions. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed. Skeletal Fractures: Among 187 adult patients who received VITRAKVI across clinical trials, fractures were reported in 7% and among 92 pediatric patients, fractures were reported in 9% (N=279; 8%). Median time to fracture was 11.6 months (range 0.9 to 45.8 months) in patients followed per fracture. Fractures of the femur, hip or acetabulum were reported in 4 patients (3 adult, 1 pediatric). Most fractures were associated with minimal or moderate trauma. Some fractures were associated with radiologic abnormalities suggestive of local tumor involvement. VITRAKVI treatment was interrupted due to fracture in 1.4% patients. Promptly evaluate patients with signs or symptoms of potential fracture (e.g., pain, changes in mobility, deformity). There are no data on the effects of VITRAKVI on healing of known fractures or risk of future fractures. Hepatotoxicity: In patients who received VITRAKVI, increased AST of any grade occurred in 52% of patients and increased ALT of any grade occurred in 45%. Grade 3-4 increased AST or ALT occurred in 3.1% and 2.5% of patients, respectively. The median time to onset of increased AST was 2.1 months (range: 1 day to 4.3 years). The median time to onset of increased ALT was 2.3 months (range: 1 day to 4.2 years). Increased AST and ALT leading to dose modifications occurred in 1.4% and 2.2% of patients, respectively. Increased AST or ALT led to permanent discontinuation in 3 (1.1%) of patients. Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Withhold or permanently discontinue VITRAKVI based on the severity. If withheld, modify the VITRAKVI dosage when resumed. Embryo-Fetal Toxicity: VITRAKVI can cause fetal harm when administered to a pregnant woman. Larotrectinib resulted in malformations in rats and rabbits at maternal exposures that were approximately 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment and for 1 week after the final dose of VITRAKVI. Adverse Reactions The most common adverse reactions (≥20%), including laboratory abnormalities, were: increased AST (52%), increased ALT (45%), anemia (42%), musculoskeletal pain (42%), fatigue (36%), hypoalbuminemia (36%), neutropenia (36%), increased alkaline phosphatase (34%), cough (32%), leukopenia (28%), constipation (27%), diarrhea (27%), dizziness (27%), hypocalcemia (25%), nausea (25%), vomiting (25%), pyrexia (24%), lymphopenia (22%) and abdominal pain (21%). Drug Interactions Avoid coadministration of VITRAKVI with strong CYP3A4 inhibitors (including grapefruit or grapefruit juice), strong CYP3A4 inducers (including St. John’s wort), or sensitive CYP3A4 substrates. If coadministration of strong CYP3A4 inhibitors or inducers cannot be avoided, modify the VITRAKVI dose as recommended. If coadministration of sensitive CYP3A4 substrates cannot be avoided, monitor patients for increased adverse reactions of these drugs. For coadministration with moderate CYP3A4 inhibitors, monitor for adverse reactions more frequently and reduce the dosage based on severity. For coadministration with moderate CYP3A4 inducers, modify dose as recommended. Use in Specific Populations Lactation: Advise women not to breastfeed during treatment with VITRAKVI and for 1 week after the final dose. Please see the full Prescribing Information for VITRAKVI ® (larotrectinib). About TRK Fusion Cancer TRK fusion cancer occurs when an NTRK gene fuses with another unrelated gene, producing a chimeric TRK protein. The altered protein, or TRK fusion protein, becomes constitutively active or overexpressed, triggering a signaling cascade. These TRK fusion proteins are oncogenic drivers promoting cell growth and survival, leading to TRK fusion cancer. TRK fusion cancer is not limited to certain types of tissues and can occur in any part of the body. TRK fusion cancer occurs in various adult and pediatric solid tumors with varying frequency, including lung, thyroid, GI cancers (colon and rectal, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS cancers (glioma and glioblastoma), salivary gland cancers (including secretory carcinoma of the salivary gland) and pediatric cancers (infantile fibrosarcoma and other soft tissue sarcomas). 4,5 About Oncology at Bayer Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated. About Bayer Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com . © 2023 Bayer BAYER, the Bayer Cross and Vitrakvi are registered trademarks of Bayer. Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com . The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments. References Hong D, et. al. Larotrectinib long-term efficacy and safety in adult patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer. ASCO Annual Meeting 2023 E-Poster. Abstract 3141. Lin, J, et. al. Long-term efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase (TRK) fusion lung cancer. ASCO Annual Meeting 2023 E-Poster. Abstract 9056. Cabanillas M, et. al. Larotrectinib (laro) long-term efficacy and safety in patients (pts) with tropomyosin receptor kinase (TRK) fusion thyroid carcinoma (TC). ASCO Annual Meeting 2023 E-Poster. Abstract 6091. Vitrakvi ® [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; December 2022. Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov . 2015;5(1):25-34. PP-VIT-US-1303-1 6/23